A functional variant of the dimethylarginine dimethylaminohydrolase-2 gene is associated with chronic kidney disease

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• 作者：Giorgio Sesti ; Gaia Chiara Mannino ; Carlo De Lorenzo ; Annalisa Greco ; Angela Sciacqua ; Maria A. Marini ; Francesco Andreozzi ; Francesco Perticone
• 关键词：Asymmetric dimethylarginine ; Chronic kidney disease ; Dimethylarginine dimethylaminohydrolase
• 刊名：Atherosclerosis
• 出版年：2013
• 出版时间：November, 2013
• 年：2013
• 卷：231
• 期：1
• 页码：141-144
• 全文大小：210 K

文摘

Objective

Studies reported a relationship between elevated asymmetric dimethylarginine (ADMA) concentrations and adverse renal outcomes. There is evidence that the rs9267551 variant in the DDAH2 gene has a functional impact with the C allele having a higher transcriptional activity resulting in increased expression of DDAH2 in endothelial cells and lower plasma ADMA levels in C allele carriers.

Methods

To address whether this variant is associated with chronic kidney disease (CDK), 2852 White European were studied. CKD was defined as estimated glomerular filtration rate (eGFR) <60?ml/min/1.73?m².

Results

The proportion of subjects with CKD was significantly lower in C allele carriers than in GG genotype carriers (OR 0.49, 95 % CI 0.25-0.97; P?=?0.03). In a logistic regression model adjusted for age, gender, BMI, blood pressure, total and HDL cholesterol, triglyceride, and fasting plasma glucose, C allele carriers have a lower risk of CKD compared with GG genotype carriers (OR 0.38, 95 % CI 0.18-0.78; P?=?0.008). This association was maintained after addition to the logistic regression model of other confounders including glucose tolerance status, presence of dyslipidemia, anti-hypertensive and antidiabetic drugs (OR 0.35, 95 % CI 0.15-0.80; P?=?0.01).

Conclusion

The rs9267551 functional variant of the DDAH2 gene is associated with CKD with carriers of the C allele having a lower risk of renal dysfunction independently from several confounders. Because ADMA predicted progression of renal disease, it is possible that, in GG carriers, ADMA may accumulate at the renal level causing endothelial dysfunction as a consequence of reduced nitric oxide availability and potentiating micro-vascular damage.